Previous studies have demonstrated that the anterior cingulate cortex modulates the activity of the autonomic nervous system, and that the posterior cingulate (retrosplenial) cortex in concert with the hippocampus plays an important role in learning and memory. When an expected result does not follow a learned responses, these regions of the limbic cortex will reduce the probability of future responses, and the mismatch will also elicit autonomic responses that will tend to alert the organism to the new conditions. Conversely, if the expected conditions are consistently present then visceromotor responses will tend to diminish. A major route by which the autonomic responses are modulated appears to be the direct projections from the posterior to anterior cingulate cortex. In the proposed studies we will directly assess this pathway electrophysiologically and determine the capacity of anterior and posterior cingulate cortex to modulate autonomic nervous system activity individually and in concert. Both cardiovascular and sympathetic nervous system responses to electrical and chemical stimulation of the midline cortex will be characterized in anesthetized and conscious rats. To elucidate the functional data generated from these studies, anatomical and physiological studies will be conducted. Our past anatomical studies have demonstrated a high degree of organization in the projections to and from the cingulate cortex and are clarifying the morphology of the neurons that contribute to the function of this cortex. The proposed studies will use a newly developed slice preparation to define the morphology of cingulate cortex neurons that have specific neuronal projections. A major focus will be on the superficial neurons which display a unique form of dendritic bundling in the retrosplenial cortex. Intracellular in vitro experiments will characterize the cortical and thalamic inputs that contribute importantly to the activity and function of the cingulate neurons. Anatomical studies will test the hypothesis that inputs terminate selectively on groups of thalamic neurons that have a common cortical projection. Both anatomical and electrophysiological experiments will delineate the influence of neuromodulators on the activity of the neurons in the cingulate cortex. These studies will elucidate the structure and function of the cingulate cortex, and the results will provide significant new information on which to base future studies on learning disorders and stress induced hypertension.